The overall objective of the research is the study of an osteoclast-activating factor (OAF) and its relationship to osteolytic neoplastic diseases and hypercalcemia. Particular emphasis will be placed on the purification and physiochemical characterization of OAF, which we have isolated from human cancer ascites fluid. The studies will also include investigations on the biological mechanism of action of OAF. We plan to develop a specific radioimmunoassay for OAF in order to establish the identity of ascites OAF with that of lymphocyte-derived OAF, to determine its cell of origin, and to evaluate the levels of OAF in patients with osteolytic lesions of the skeleton and cancer-related hypercalcemia. Recent studies on the mechanism of action of the bone resorptive protein demonstrate that this protein stimulates matrix resorption in vitro and also mobilizes calcium in vivo. Moreover, the protein, on the basis of in vitro studies, appears to act through the stimulation of prostaglandin synthesis. (W)